In our article (1), the recommendations for and dosing of the drugs to treat Clostridium difficile infection are based on the current European guidelines (2). However, treatment with oral metronidazole requires some minor modification to reflect the special situation in Germany where the oral formulation of metronidazole contains only 400 mg. With no oral 500 mg formulation available, uncomplicated Clostridium difficile infection (CDI) should be treated with 400 mg four times a day (1600 mg daily) instead with the internationally recommended oral metronidazole dose of 500 mg three times a day (1500 mg daily).
Frequently, questions about vancomycin-tapering treatment for relapse are asked. The proposed regime is based on the few case series available (2, 3) and starts after the 2-week induction therapy with an oral vancomycin dose of 250 mg four times daily. The tapering period starts with an oral vancomycin dose of 250 mg twice a day over 7 days, followed by an oral dose of 250 mg once a day for further 7 days. Subsequently, the patient is treated with oral doses of 250 mg every 48 hours (altogether 4 doses), followed by oral doses of 250 mg every 72 hours (five doses).
Regarding the epidemiology of C. difficile—We appreciate Professor Stausberg’s comment on the epidemiological significance of C. difficile in Germany which is still underestimated. The evaluation of routine data from the DRG system (Institute for the Hospital Remuneration System, INEK) and health insurances definitely help to estimate the incidence density rate (4). However, prompt detection of infection and outbreak events with the potential to respond can only be achieved when CDI becomes a notifiable disease based on mandatory reporting strategies; some European countries have already embraced and done this step.
Optimization of microbiota transfer—Microbiota transfer (“stool transplantation“) for relapsing CDI is an attractive causal treatment. Our review showed that both antegrade and retrograde application are feasible options for microbiota transfer; here the advantages and disadvantages of the two routes of application are to be considered based on personal experiences, as highlighted by Dr. Ehlermann. Consequently, the best route of application should be decided individually for each patient, taking into account the special experiences of the center and any risk factors the patient may have. It can be expected that in the next years microbiota transfers will be further simplified and optimized, and defined bacterial mixtures will be approved as oral medicines in the future. As a first step to simplify the application of donor microbiota, fecal samples will be packed and cryopreserved in capsules for easy oral administration (5). This approach has the potential to achieve a comparable treatment success without invasive interventions.
Dr. med. Christoph Lübbert
Fachbereich Infektions- und Tropenmedizin
Klinik und Poliklinik für Gastroenterologie und Rheumatologie
Department für Innere Medizin
Neurologie und Dermatologie
Dr. med. Endres John
Klinik für Allgemein-, Viszeral- und Gefäßchirurgie
Universitätsklinikum Halle (Saale)
Prof. Dr. med. Lutz von Müller
Medizinische Mikrobiologie und Hygiene
Institute für Infektionsmedizin
Konsiliarlabor Clostridium difficile,
Universitätsklinikum des Saarlandes
Conflict of interest statement
Dr. Lübbert has received reimbursement of conference fees from Novartis, MSD, and Astellas. Novartis and Astellas have paid travel expenses for him. He has received lecture fees from Novartis, InfectoPharm, MSD, and Astellas.
Prof. von Müller has received conference fees and reimbursement of travel expenses from Novartis and Astellas. He has received lecture fees from Astellas, Pfizer, Novartis, and Diasorin. He has received trial funding (third-party funds) from Astellas, Diasorin, BD, and Great Basin.
Dr. John declares that no conflict of interest exists.
|1.||Lübbert C, John E, von Müller L: Clostridium difficile infection – guideline-based diagnosis and treatment. Dtsch Arztebl Int 2014; 111: 723–31 VOLLTEXT|
|2.||Debast SB, Bauer MP, Kuijper EJ: European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2014; 20: 1–26 CrossRef MEDLINE|
|3.||McFarland LV, Elmer GW, Surawicz CM: Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease. The American Journal of Gastroenterology 2002; 97: 1769–75 CrossRef MEDLINE|
|4.||Stausberg, J: International prevalence of adverse drug events in hospitals: an analysis of routine data from England, Germany, and the USA. BMC Health Services Research. 2014; 14: 125 CrossRef MEDLINE PubMed Central|
|5.||Youngster I, Russell,GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL: Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA 2014; 312: 1772–8 CrossRef MEDLINE|